High-grade gliomas (HGGs) are a diffusely infiltrating group of cancers with dire prognoses. The lateral ventricle subventricular zone (SVZ) stem cell niche is thought to be a tumor reservoir for a range of HGGs including adult glioblastoma (GBM). Glioma contact of neural stem cell niches, particularly the subventricular zone, has been closely associated with decreased survival (Chaichana et al. (2008) J. Neurooncol. 89, 219-224; Jafri et al. (2013) Neuro. Oncol. 15, 500 91-96; Mistry et al. (2017) J. Neurooncol. 131, 125-133; Mistry et al. (2017) J. Neurooncol. 132(2):341-349) and increased tumor recurrence (Adeberg et al. (2014) Int. J. Radiat. Oncol. Biol. Phys. 90, 886-893; Chen et al. (2015) Radiother. Oncol. 116, 294-300). Diffuse intrinsic pontine glioma (DIPG; recently re-classified as diffuse midline glioma, H3K27M mutant (Louis et al. (2016) Acta Neuropathol. 131, 803-820) is the most common HGG of childhood and the leading cause of pediatric brain tumor-related death, with a median survival of only 9 months and a 5-year survival of less than 1% (Donaldson et al. (2006) J. Clin. Oncol. 24(8), 1266-1272). DIPG tends to not only infiltrate the brainstem, where it originates, but also the forebrain, with a particular propensity for spread to the SVZ, which occurs in ˜65% of cases (Caretti et al. (2014) Acta Neuropathol. 128, 605-607). A point of debate regarding SVZ involvement in adult GBM has been whether gliomas spread to the SVZ or whether the cancer originates there. In DIPG, the tumor clearly begins in the pons and from some anatomical distance spreads to the lateral ventricle SVZ, clarifying the propensity of HGGs to travel to the SVZ niche. DIPG is thus an illustrative tumor type in which to discern the mechanisms of SVZ invasion that may be broadly relevant to HGGs.
There remains a need for better methods of treating glioma, particularly to limit SVZ invasion.